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Devils' advocates. Captive-population breeders could use the recently sequenced Tasmanian devil genome to help foster future generations that are resistant to a parasitic cancer that's pushed the animal to the brink of extinction.

Stephan Schuster

For Conservationists, the (Tasmanian) Devil Is in the Details

As a transmissible cancer rips through the wild Tasmanian devil population, first deforming the marsupials and then killing them, geneticists are racing to find genes that they hope will help prevent the species's looming extinction. Captive breeding programs have been working without a genetic cheat sheet to guide their decisions about which individual devils to breed to foster cancer resistance. Now, the first published whole-genome sequencing of the devil's DNA might enable conservationists to build a better devil and save the species.

Scientists first noticed devil facial tumor disease (DFTD) in 1996. The stocky marsupials, which once ranged throughout the Australian islands but today are only found on Tasmania, began showing up in the northeastern part of the island with ugly, lethal tumors. Since then, the disease has spread throughout the island's devils, killing off as many as 90% of them in some areas. The total wild population is down to about 40,000 individuals, compared with more than 100,000 before the DFTD outbreak.

The cancer spreads parasitically—one of only a handful of malignancies known to do so—jumping from devil to devil when the animals bite one another, touch faces, or mate with one another.

"It's the only known case where cancer is just burning through a wild population," says Stephan Schuster, a conservation biologist at Pennsylvania State University, University Park, and co-author of the new study, published online today in the Proceedings of the National Academy of Sciences (PNAS).

The cancer takes advantage of the devil's extremely low genetic diversity, Schuster says. Most animals, including humans, can't simply transplant tissue, including cancerous tissue, between individuals, but Tasmanian devils' geographical isolation and inbreeding has made them all very closely related. That not only fosters transmission of the cancer, Schuster says, but also makes it more difficult for the devils to mount an immune response. Genetic mixing over time can allow evolution to select for more resistant offspring; little mixing means little resistance.

Biologists have speculated that there may be enough genetic diversity left within the Tasmanian devil population to ward off the disease, but the devils' normal mating patterns won't be enough. Captive breeding programs, already in place to preserve cancer-free individuals, could encourage genetic mixing and even select for specific cancer-resistant genes if they knew which genes to look for, Schuster says.

To that end, he and colleagues sequenced the genomes of two devils, Cedric and Spirit. Cedric, a devil from Tasmania's northwestern corner, resisted two different strains of DFTD before finally succumbing to a third strain, indicating that some of his genes might be valuable in the fight against the cancer. Spirit, from the southeast, was found near death in the wild and died shortly after. They represent the island's geographical extremes and offer scientists the best look at the population's overall genetic diversity.

Schuster and his team also analyzed Spirit's tumor and compared its genome with her own and Cedric's to determine which genes belonged to the disease and which belonged to the individual devils.

Looking at where Cedric's genome diverged from Spirit's, the scientists identified three key mutations to Spirit's genome that affect cell cycle regulation, or the rate at which cells die. There are likely many other genes involved, Schuster says, but these are a promising start in determining which genes affect cancer resistance.

The researchers then identified seven geographic regions where devil populations are the most genetically diverse. Captive breeding programs should assemble their breeding populations from equal numbers of devils from these seven locations, they recommend in their PNAS study.

If all goes according to plan, Schuster says, the Tasmanian devil population could rebound and become self-sustaining again within as few as two or three generations.

The scientists also analyzed DNA from hundreds of museum-specimen Tasmanian devils stretching back hundreds of years. The devils' low genetic diversity dates back about 100 years, they found, after farmers exterminated many of the predators that threatened their livestock.

"Cancer is a freak occurrence of evolution," Schuster says. "There's no reason for this species to be wiped off the face of the planet because human activity artificially reduced its genetic diversity."

Hamish McCallum, a conservation biologist at Griffith University in Brisbane, Australia, and a former senior scientist at the Save the Tasmanian Devil Program, agrees that targeted captive breeding programs could be useful in saving the animals from extinction.

"It's probably about the best prospect we've got so far," he says. Conservationists should be careful to preserve as much genetic diversity as possible and not just select for DFTD-resistant genes, though, McCallum cautions, as those genes might prove vulnerable to some future threat.